Juno’s lead CAR-T slammed with a clinical hold in the last lap ahead of FDA filing

by John Carroll — on July 7, 2016 04:34 PM EDTUpdated: December 30, 2016 06:18 PM

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One of Juno’s critical studies for its lead CAR-T therapy has just been indefinitely sidelined following the unexplained death of two patients from neurotoxicity, derailing the company’s plans to seek marketing approval in time for a 2017 launch.

In a nasty surprise for shareholders, Juno announced Thursday afternoon that the FDA had placed a clinical hold on its ROCKET study, a Phase II clinical trial of JCAR015 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia. That hobbles the company just as it entered the last lap in a tight race with Kite Pharma.

In a call with analysts, Juno CEO Hans Bishop said that the company no longer expects to get the drug on the market in 2017. That deadline has now been pushed to 2018. He also said that another patient had died of neurotoxicity in May, but the study continued after discussions with the FDA. All the patients who died were young.

The biotech instantly pointed to the recent addition of fludarabine as part of the pre-conditioning regimen patients undergo as a likely cause of the deaths. And they have already proposed dropping that.

“Fludarabine in some ways acts like a dose amplifier,” says Bishop, explaining the company’s theory of what went wrong and triggered these cases of cerebral edema.

The FDA has asked for: “A revised patient informed consent form, a revised investigator brochure, a revised trial protocol, and a copy of the presentation made to the agency yesterday.”

All other studies are continuing. And a submission is already expected to be submitted this week, underscoring the company’s belief that it can get the hold lifted quickly.

There are absolutely no guarantees, however, that that can be done. Zafgen has been waiting for months for regulators to address their clinical hold. And regulators are known for taking their time in resolving these issues.

That’s a huge issue for Juno, which was telling reporters just weeks ago that it was confident of filing for an accelerated approval in time to get their drug on the market next year — racing with Kite to be the first on the market. It may also affect other programs as well, if Juno is right. Recent research has indicated that adding fludarabine improves CAR-T cell expansion and persistence, providing what was thought to be an added edge in treating cancer.

Arch managing partner and Juno director Robert Nelsen took to Twitter to defend the company.

JUNO. The road to cancer cure is not easy. Condolences to the heroes in clinical trials and Hope for those who get such promising therapies.

Juno captured public attention with its pioneering work on CAR-Ts, taking patient cells and adapting them with a chimeric antigen receptor to make them into cancer cell attack vehicles. Early on investigators had to adjust their studies to counter the chance that patients would be hit with a cytokine storm as the drug was administered. This is the first time that neurotoxicity has halted a CAR-T study.

And where does this leave Kite? Clearly in the lead.

The biotech put out a release late Thursday asserting that it completed enrolling patients for its ongoing Phase II pivotal study of KTE-C19, leaving it on track for a submission to the FDA by the end of the year.

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